Arsenic compounds of phenyl-hydrazo-naphthol sulfonic acids



Patented Apr. 22, 1947 ARSENIC COMPOUNDS OF PHENYL-HY- DRAZO-NAPHTHOLSULF-ONIC ACIDS Ernst A. H. Friedheim, New York, N. Y.

No Drawing. Application October 31, 1942, Serial No. 464,079

4 Claims. (01. 260-440) This invention relates to hydrazo-compounds andtheir derivatives, said compounds and derivatives .containing residuesof naphthalene sulfonic acid derivatives and residues of phenyl-arseniccompounds containing trivalent and pentavalent arsenic. The compoundsaccording to this invention comprise one or two systems of the followinggeneral formula: Y

In this formula G is selected from the group consisting of H and -SO3H;

C6 represents abenzene nucleus;

Y i selected from the group consisting of -OI-I, NI-I2, NI-Iacyl,-NHalkyl, -NHCOzalkyl, O-alkyl, -O--CO2alkyl, -Oacyl;

A and B may be the same or different and are selected from the groupconsisting of I-I, OH, -Oalkyl, Oacyl, Cl, Br, F, I, -NO2, alkyl, NH2,NHalkyl, NHacyl, --NHNH2, NH-NHacyl, --NacylNH2, --NacylNHacyl,NH-'-NHalkyl, NalkylNI-I2,

D is selected from the group consisting of O3H2, =0, =halogenz', =5,radicals of the formula SOaH and radicals of the formula =(SR)2, whereinR stands for any aliphatic or aromatic cyclic group capable of carryinga --SI-I- group, such as thicglycolic acid and thiophenol;

The group -AsD may be in ortho-, metaor para-position to thehydrazo-linkage;

The nitrogen atoms of the hydrazo-linkage may beconnected by the freevalencies indicatedin the above Formulas'I and II to H atoms or to astabilizing radical or radicals taking the place of one or both of theseH atoms and being capable of stabilizing the hydrazo-compounds. Both Natoms of the hydrazo-linkage may be connected to one and the samestabilizing radical or each N atom may be connected to an individualstabilizing radical. In the latter case these radicals may be the sameor different. The monoor divalent stabilizing radicals are selected fromthe group consisting of alkyl, monoand divalent acyl radicals, residuesof aliphatic or cyclic carbonyl radicals, and aliphatic or cyclicisocyanate radicals.

The compounds embodying the present inven tion are colorless or slightlyyellowish substances, readily soluble in water, insoluble in benzene andchloroform.

They have a distinct therapeutic effect in diseases caused by certainspirochetes and protozoa. They'difiuse readily into the body fluids,including the liquid media of the eye and the cerebrospinal fluid. Theyhave no toxic effect on the central nervous system.

The hydrazo-compounds according to the present invention may be preparedby appropriate reduction of the corresponding azo-dyes, preferably bymeans of Zn or Fe dust, in alkaline solu- .tion. The correspondingazo-dyes may be prepared:

(a) By coupling according to classical methods an aromaticdiazo-compound containing a radical of trior pentavalent arsenic withthe desired naphtholor naphthyl-amine-deriva tive;

(b) By condensing a phenylhydrazine-derivative containing a radical oftrior pentavalent arsenic radical with a 1,2-naphthoquinone-sulionicacid derivative;

(0) By coupling a diazotized .p-naphthylaminesulfonic acid derivativewith a phenyl-arsenic derivative containing .a trior pentavalent arsenicradical and a hydroxyand/or aminogroup. 4

Hydrazo-compounds according to this invention, in which the nitrogenatoms of the hydrazo-linkage carry an H atom, reduce ammoniacal silversolution. They are in alkaline and neutral aqueous solution relativelysensitive to molecular oxygen, by which they are oxidized tothecorresponding azo-dyes.

3 Such hydrazo-compounds may be stabilized against the action ofmolecular oxygen by substituting for the H atom of the hydrazo-linkage astabilizing radical. Thus, stabilized hydrazocompounds may be obtainedby monoor dialkylation and acylation, the stabilized compoundscontaining for example, the following linkages between the naphthaleneand benzene nucleus:

--N(COCH3)--N(COCH3) N (COzalkyl) -N (COzalkyl) N(COCcH)N(COCsI-I5)- N(COCHs) NH -N (COzalkyl) NH N (COCsHs) NH- The hydrazo-compoundscontaining H atoms in the hydrazo-linkage may also be stabilized bycondensation with carbony1 compounds, such as aliphatic or cyclicaldehydes and ketones. -Suchcarbonyl compounds, which form divalentradicals, may condense with one hydrazo-compound to form derivativescarrying a linkage between the naphthalene and benzene nucleus, such asin the case of acetaldehyde:

or one carbonyl compound may combine with 2 hydrazo derivatives so thatthe linkages between naphthalene and benzene nucleus take, for exampleby reaction with formaldehyde, the following form:

' N|NH- N-NH- d $H2 $Hg N N v Two molecules of a hydrazo derivative mayalso belinked together by reaction with an acid chloride of a dibasicacid such as malonyl dichloride according to the following scheme:

slam

Such an acid dichloride derived from a dibasic acid may also condensewith one molecule of a hydrazo-compound to form, i. e. in the case ofmalonyl dichloride, a stabilized hydrazo derivative of the followingtype:

Stabilization may further be obtained by reacting the hydrazo-compoundswith isocyanic acid and its derivatives to form compounds carrying i. e.the following groups:

and furthermore, by addition of acetylenedicarboxylic acid esters, toform compounds 1. e. according to the following formula:

I denote all such radicals taking the place of H atoms of thehydrazo-linkage and being capable of stabilizing hydrazo-compoundsembodying my present invention, by linking said radicals to the N atomsof the hydrazo-linkage, as stabilizing radicals.

Example I .-53.1 g. of the red azo-dye obtained by coupling diazotizedarsanilic acid with u-naphthol-4,8-disulfonic-acid, according to U. S.Patent No. 2,244,293 is dissolved in 700 cc. of N/l NaOH and treatedwith 100 g. of Zn dust, until the red solution is decolorized. Thereaction mixture is filtered from the Zn sludge, acidified with aceticacid and salted out. The monosodium salt of [benzenearsonic acid (4)]-(l-hydrazo-2)- [naphthol (1) disulfonic acid (4,8)] forms then ayellowish precipitate, which may be crystallized out of warm water in anatmosphere of hydrogen. The new compound forms a slightly yellowishcrystalline powder, which is soluble in water, insoluble in chloroformand ether. Its alkaline solution turns red on shaking with air.

Replacing in the foregoing example arsanilic acid by4-oxy-3-aminophenylarsonic acid and proceeding otherwise in the samemanner, [(4)- oxyphenylarsonic acid] (3-hydrazo-2)[naphthol(l)-disulfonic acid(4,8)l is obtained.

Example II.-61.2 g. of the azo-dye obtained by coupling diazotizeda-naphthol-amino-(2)- trisulfonic acid-(4,6,8) withp-hydroxy-phenylarsinoxide (or by coupling diazotized (3)-amino-(4)hydroxy-phenylarsinoxide with oz-liaDhthOl- (4,6,8) trisulfonic acid)is dissolved in 15 parts of 20% aqueous ammonia and treated with acurrent of HzS, until the solution is decolorized. On cooling theammonium salt of [(4)-hydroxyphenylarsinsulfide](3-hydrazo-2) unaphthol- (4,6,8) trisulfonic acid forms a yellowish precipitate, whichis filtered off and dissolved in 5 parts of 10% acetic acid. The sodiumsalt is precipitated from this solution by salting out with sodiumchloride. The corresponding arsinoxide is obtained by dissolving the newcompound in an excess of aqueous sodium hydroxide in an atmosphere ofhydrogen, acidifying with acetic acid and salting out with sodiumchloride.

Example I1I.-50 g. of the azo-dye obtained by couplingp-diazobenzenearsinoxide with a-naphthol-(4,8)-disulfonic acid aredissolved in 700 cc. of N/l NaOH and treated with iron powder, until thesolution is decolorized. The reaction mixture is quickly filtered fromthe iron sludge and shaken in an atmosphere of hydrogen with 45" g.';ofbenzoylchlor'ide', which is added in succes amazes sivejsmall portions.'On acidification 'withacetic acid andsaturation with sodium chloride:the sodium salt of the following acid forms a white, slightly:yellowishprecipitate of theiormula:

SOaH

Example IV. 53.2 g. of .[benzenearsonic acid (*4)l-(l-hydrazo-2)-[naphthol (1) disulfonic acid-(4,8)] prepared according to Example 1,are dissolved in 800 cc. of N /1 NaOH and treated, in an atmosphere ofhydrogen, with '35 g. of chlorocarbonic iethylester. On acidificationwith acetic acid andsaturation with sodium chloride, the sodium salt ofthe following acid forms a white, faintly yellowish precipitate:

$0311 OOzCzHs SOQH drogen, in thepresence of 100 g. of finely divided 4calcium carbonate with 16 g. of benzoylchloride, at a temperature notexceeding20 C. On acidification with acetic acid and on addition ofsodium acetate, the monosodium salt of the following acid forms a whiteprecipitate, which is filtered off:

SOaH

washed with concentrated sodium acetate solution, alcohol and ether.

By replacing in the above example the benzoylchloride by 60 cc. of a 20%solution of malonyldichloride in chloroform, a compound of the followingformulais obtained:

Example VI.53.4= g. of [benzenearsonicacid(4)l-(l-hydrazo-2)Jot-naphthol (4,8) disulfonic acid] are dissolved,with addition of 25.8 g. of sodiumbicarbonate, in 300 0c. of water, andshaken in an atmosphere of hydrogen with 5 g.

of acetaldehyde. On acidification with acetic acid "6 and cooling, awhite precipitate:oi'thefollowing construction is :formed, filtered off,washed with ice-cold .dilute acetic acid, alcohol and .ether:

SOaH OH N\-NC As0aHz a CHa $0311 By replacing in the foregoing examplethe acetaldehyde by 25 cc. of neutral 30% formaldehyde, a whiteprecipitate of the following .formulais formed:

son; OH

TT' AsOsH2 SOsH l H2 CH2 SOaH OH I SOBH Example VII.-1 part of[(4)hydroXy-Dhenylarsinoxide ('1) -(3 hydrazo 2) [a naphthol- (4,-8)disulfonic acid], "prepared according to 'a procedure in all'waysanalogous to that described in Example 2, is suspended in 10 parts ofacetic anhydride. The reaction mixture is shaken at a temperature notexceeding 15 C. 25 parts of'ice are added. The suspended material isthen filtered off and washed with acetic acid, alcohol and ether. Thewhite substance thus obtained is [(4) hydroxy phenylarsinoxide(l)](3-monoN- acetyl hydrazo) -2- [a naphthol 4,8) disulfonic acid].

' By running the acylation with an excess of acetic anhydride atatemperature-of -.100 C., the corresponding diacetyl-derivative isobtained, i. e. a[(4)-hydroxy-phenylarsinoxide-(1)]- (3-di- N-acetylhydrazo) -2-[a-naphthol-(4,8) disulfonic acid].

Example VIII .---53.3 g. of [benzenearsonic acid (4)1-(1 hydrazo 2)[naphthol(l) disulfonic acid (4,8)] is dissolved with 25.8 g. of sodiumcarbonate in 500 cc. of water and treated with 25g, ofphenylisocyanate.On acidification with-acetic acidand cooling, a white precipitate ofthefollowingconstitution is-formed and filtered off:

S0311 OH (I30 ('30 NH NH Example IX.53 g. of the azo-dye obtained bycoupling diazotized m-arsanilicacid with u-naphthylamine-lfi disulfonicacid are dissolved in 500 cc. of tN/ 1 NaOI-I and treated with g. ofiron powder until the reaction mixture-is decolorized; The reactionmixture is filtered and. shaken with 30g. .of dimethyl-sulfate, which is.added'in successivle portions. 'Onacidification withacetioacidandsatur-ation*withsodiumchloride, a wh1te.tpre-..

cipitate is obtained, which is filtered ofi and washed with concentratedaqueous sodium acetate, alcohol and ether, and which is of the followingformula:

SOsH NHCH;

an. en.

Exmaple X.One of the azo-dye obtained by coupling diazotized(1)hydroXy-(2)diazo-naph- 15 th'alene-(4,8) disulfonic acid in alkalinesolution with (4)oxy-phenylarsinoxide is dissolved in 12.7 parts of NlNaOH and treated with 1.5 parts of Zn dust, until the reaction mixturebecomes colorless. The reaction mixture is then filtered, acidified withacetic acid and salted out. A slightly yellowish precipitate of[(1)naphthol- (4,8)disulfonic acid] (2 hydrazo-3')(Rhydroxyphenylarsinoxide(1) is obtained, which is filtered off, washedwith concentrated aqueous sodium acetate, alcohol and ether.

Example XI.-One part by weight of 4,l'-dihydroxy arsenobenzene-3,3-bis[azo-2l-naphthol-(l) -disulfonic-4,8-acid prepared as described in myprior Patent No. 2,235,478 is dissolved in 15 parts B. W. of aqueous2.8% bicarbonate of soda solution and subjected to the action of 4 partsB. W. of Zn dust at ordinary room temperature. The compound formed hasthe formula:

SOaH OH OH SOaH SOaH 80:11

It can be precipitated from the solution by acid and can be stabilizedby redissolving in dilute aqueous alkali and reacting it i. e. withchlorocarbonic methylester.

Example XII.-A stabilized hydrazo compound containing an arseno-group isobtanied by reducing an acetylated trivalent arsenic compound preparedaccording to Example VII with sodium hydrosulfite to the correspondingarsenoderivative.

Furthermore, stabilized hydrazo-compounds accordin to the presentinvention may be obtained by reducing stabilized hydrazo-compoundscontaining pentavalent arsenic radicals of the type described in ExampleIV with sodium hydrosulfite to the corresponding arseno-compounds.

Example XIII.-An azo-compound of the formula 2 SOsH S0311 OH 8 linesolution' This hydrazo-compound may be stabilized by treatment withphenylisocyanate according to Example VIII.

In a substantially similar manner compound of the formula a hydrazo-SOzH OH S 03H 0 H O H AsO wherein G is selected from the groupconsisting of H and 803K.

2. A hydrazo-compound corresponding to the formula SOaH OH HN-NHQ-ASOSOaH wherein G is seelcted from the group consisting of H and 303K.

3. A hydrazo-compound corresponding to the formula SOaH OH SOaH whereinG is selected from the group consisting of H and 8031-1; A and B areselected from the group consisting of H and OH; and AsD is selected fromthe group consisting of arsonic acid radicals, As O and arseno-radicals.

4. A hydrazo-compound of the general for- SOaH OH BOaH wherein G isselected from the group consisting of H and SOsH; A and B are selectedfrom the group consisting of H and OH; and --AsD is selected from thegroup consisting of arsonic acid radicals, As=O and arseno-radicals,and. W and. W are selected from the group consisting of hydrogen andalkyl radicals.

ERNST A. H. FRIEDHEIM.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS Number Name Date 1;932,152 Zitcher et a1 Oct. 24,1933 2,295,565 DAlelio et a1 Sept, 15, 1942 2,244,293 Friedheim June 3,1941 2,235,478 Friedheim Mar. 18, 1941 OTHER REFERENCES Raiziss et 2.1.,Organic Arsenic Compounds" (1923),p. 257.

Gattermann, The Practical Methods of Organic Chemistry (1896), pp. 184and 185.

